DERIVATIVES OF 1-(2-OXOACETYL)-PIPERIDINE- OR PYRROLIDINE-2-CARBOXYLIC ACIDS, PHARMACEUTICAL COMPOSITION, METHOD OF TREATMENT, METHOD OF SYNTHESIS

摘要

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention describes the novel derivatives of 1-(2-oxoacetyl)-piperidine- or pyrrolidine-2-carboxylic acids of the general formula (I) where A is oxygen atom; B and D mean independently Ar, direct or branched (C₁-C₁₀)-alkyl, direct or branched (C₂-C₁₀)-alkenyl or (C₂-C₁₀)-alkynyl; Ar means direct or branched substituted (C₁-C₆)-alkyl, direct or branched (C₂-C₆)-alkenyl or (C₂-C₆)-alkynyl being in each case one of CH₂-groups of indicated alkyls, alkenyls or alkynyls can be optionally substituted with oxygen atom or the group of the formula (ii) where Q means hydrogen atom or direct or branched (C₁-C₆)-alkyl; T means Ar or 5-7-membered cycloalkyl substituted with hydroxy-group at position 4 under condition that at least one of B and D is taken independently from the group including direct or branched (C₂-C₁₀)-alkynyl; Ar means direct or branched substituted (C₂-C₆)-alkynyl where Ar means phenyl, 2-thienyl, 2-, 3- or 4-pyridyl, benzimidazolyl, 3H-indolyl, purinyl, 7-aza-indolyl and Ar can contain optionally 1-3 substituents taken independently among the group including hydroxy-group, hydroxymethyl-group, direct or branched O-(C₁-C₄)-alkenyl, O-phenyl, O-benzyl, carboxy-group, direct or branched N,N-di-C₁-C₅-alkyl, carboxamide, N-benzylcarboxamide, morpholinecarbonyl, thiomorpholinecarbonyl, N-methyl- or N-benzylpiperazinocarbonyl or the group of the formula -O-(CH₂)_q-X where X means 2-, 3- or 4-pyridyl, pyrazinyl or 2- or 3-thienyl; q is a whole number 0-2 where L means U and M means oxygen atom; U means direct or branched (C₁-C₆)-alkyl or Y where Y can contain optionally 1-3 substituents taken independently among the group consisting of direct or branched O-(C₁-C₄)-alkyl, O-benzyl, O-phenyl, direct or branched O-(C₂-C₄)-alkenyl, 1,2-methylenedihydroxy-group or 3-phenyl-(E)-prop.- -2-enyl; n = 1 or 2; m is a whole number 0-3. Novel compounds of the formula (I) maintain, enhance or recover sensitivity of cells to therapeutic or prophylactic agents. Invention relates to also pharmaceutical composition containing these compounds. These compounds and pharmaceutical compositions can be used for treatment of cells showing resistance to effect of many drugs, prevention of development of resistance to many drugs and for therapy of cancer disease showing resistance to many drugs. Invention describes also method of treatment and method of synthesis of compounds of the formula (I). EFFECT: new compounds indicated above, improved method of synthesis and treatment, valuable medicinal properties. 13 cl, 2 tbl, 13 ex